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We applied four fractal dimension estimation algorithms on the temporal electrical impedance signal of normal MDCK type II cell cultures monitored by ECIS technique and showed that the fractal dimension due to micromotion allows discriminating processes not sensed by the spectral impedance of the culture. In this work we subjected cell cultures to electric current damage and drug exposure to analyze the changes in the fractal structure of the temporal signal. Among the changes presented and detected are the differentiation between a healthy monolayer and one exposed to a drug, as well as the distinction between a seeding process and a wound-healing process performed by electric current. The four algorithms used were validated by applying them on topological functions of known fractal dimension, a study that determined the necessary conditions for a correct estimation.

Abstract Studying animal models furthers our understanding of Parkinson’s disease (PD) pathophysiology by providing tools to investigate detailed molecular, cellular and circuit functions. Different versions of the neurotoxin-based 6-hydroxydopamine (6-OHDA) model of PD have been widely used in rats. However, these models typically assess the result of extensive and definitive dopaminergic lesions that reflect a late stage of PD, leading to a paucity of studies and a consequential gap of knowledge regarding initial stages, in which early interventions would be possible. Additionally, the better availability of genetic tools increasingly shifts the focus of research from rats to mice, but few mouse PD models are available yet. To address these, we characterize here the behavioral, neuronal and ultrastructural features of a graded-dose unilateral, single-injection, striatal 6-OHDA model in mice, focusing on early-stage changes within the first two weeks of lesion induction. We observed early onset, dose-dependent impairments of overall locomotion without substantial deterioration of motor coordination. In accordance, histological evaluation demonstrated a partial, dose-dependent loss of dopaminergic neurons of substantia nigra pars compacta (SNc). Furthermore, electron microscopic analysis revealed degenerative ultrastructural changes in SNc dopaminergic neurons. Our results show that mild ultrastructural and cellular degradation of dopaminergic neurons of the SNc can lead to certain motor deficits shortly after unilateral striatal lesions, suggesting that a unilateral dose-dependent intrastriatal 6-OHDA lesion protocol can serve as a successful model of the early stages of Parkinson’s disease in mice.

Abstract Background Peripheral nerve stimulation is used in both clinical and fundamental research for therapy and exploration. At present, non-invasive peripheral nerve stimulation still lacks the penetration depth to reach deep nerve targets and the stimulation focality to offer selectivity. It is therefore rarely employed as the primary selected nerve stimulation method. We have previously demonstrated that a new stimulation technique, temporal interference stimulation, can overcome depth and focality issues. Methods Here, we implement a novel form of temporal interference, bilateral temporal interference stimulation, for bilateral hypoglossal nerve stimulation in rodents and humans. Pairs of electrodes are placed alongside both hypoglossal nerves to stimulate them synchronously and thus decrease the stimulation amplitude required to activate hypoglossal-nerve-controlled tongue movement. Results Comparing bilateral temporal interference stimulation with unilateral temporal interference stimulation, we show that it can elicit the same behavioral and electrophysiological responses at a reduced stimulation amplitude. Traditional transcutaneous stimulation evokes no response with equivalent amplitudes of stimulation. Conclusions During first-in-man studies, temporal interference stimulation was found to be well-tolerated, and to clinically reduce apnea-hypopnea events in a subgroup of female patients with obstructive sleep apnea. These results suggest a high clinical potential for the use of temporal interference in the treatment of obstructive sleep apnea and other diseases as a safe, effective, and patient-friendly approach. Trial registration The protocol was conducted with the agreement of the International Conference on Harmonisation Good Clinical Practice (ICH GCP), applicable United States Code of Federal Regulations (CFR) and followed the approved BRANY IRB File # 22-02-636-1279.

Obesity is a heterogeneous disease that affects almost one-third of the global population. A clear association has been established between obesity and cardiovascular disease (CVD). However, CVD risk is known to be related more to the local distribution of fat than to total body fat. Visceral adipose tissue (VAT) in particular has a high impact on CVD risk. This manuscript reviews the role of VAT in residual CV risk and the available therapeutic strategies for decreasing residual CV risk related to VAT accumulation. Among the many pathways involved in residual CV risk, obesity and particularly VAT accumulation play a major role by generating low-grade systemic inflammation, which in turn has a high prognostic impact on all-cause mortality and myocardial infarction. In recent years, many therapeutic approaches have been developed to reduce body weight. Orlistat was shown to reduce both weight and VAT but has low tolerability and many drug-drug interactions. Naltrexone-bupropion combination lowers body weight but has frequent side effects and is contraindicated in patients with uncontrolled hypertension. Liraglutide and semaglutide, glucagon-like peptide 1 (GLP-1) agonists, are the latest drugs approved for the treatment of obesity, and both have been shown to induce significant body weight loss. Liraglutide, semaglutide and other GLP-1 agonists also showed a positive effect on CV outcomes in diabetic patients. In addition, liraglutide showed to specifically reduce VAT and inflammatory biomarkers in obese patients without diabetes. GLP-1 agonists are promising compounds to limit inflammation in human visceral adipocytes.

El artículo examina los dos relatos que la Biblioteca ofrece de los que Céfalo es protagonista, destacando la coherencia interna de cada uno de ellos, así como la independencia de uno respecto al otro. Dentro de las genealogías atenienses, Céfalo es el desafortunado esposo de Procris: es víctima del carácter amenazante de su mujer y del poder nefasto de sus regalos. En el episodio de la caza de la zorra cadmea, que precede a la concepción de Heracles, el relato destaca el carácter prodigioso del perro, esencial en el plan de Zeus, y el destino de Céfalo, que se convierte en un héroe fundador.

Introducción: Se estima que 8% de la población experimenta dificultad para consumir alimentos sólidos y líquidos. Los pacientes con dieta de textura modificada suelen tener ingesta alimentaria variable. Objetivos: Medir el grado de adecuación a los requerimientos calóricos y proteicos en pacientes hospitalizados con dietas de textura modificada IDDSI niveles 4, 5 y 6. Determinar si existe asociación entre el porcentaje de adecuación y los niveles de textura. Materiales y métodos: Se evaluó la ingesta mediante un método de desperdicio de plato de 3 días. Los valores calóricos y proteicos fueron comparados con las IDR según estado nutricional. Se calculó el porcentaje de adecuación calórico y proteico. El análisis estadístico se realizó utilizando el Test de Kruskal Wallis para la comparación de medias según nivel IDDSI. Resultados: La muestra quedó conformada por 52 pacientes hospitalizados mayores de 18 años con indicación de dieta de textura modificada. La media del porcentaje de adecuación calórica fue 72,31%, 79,35%, 83,9 % para IDDSI 4, 5 y 6 respectivamente. La adecuación proteica fue del 71,89%, 77,25% y 80,75% para IDDSI 4, 5 y 6 respectivamente. Conclusiones: No existen diferencias estadísticamente significativas en el grado de adecuación calórica y proteica en cada uno de los grupos según los niveles de IDDSI. Se observa una tendencia a presentar un mayor porcentaje en la adecuación a los requerimientos tanto calóricos como proteicos a medida qué se incrementan los niveles de IDDSI. Palabras clave: IDDSI, adecuación a requerimientos calórico-proteicos, dieta de textura modificada.

Introducción: Se hace necesario pensar en la alimentación y sus prácticas, más allá de sus propósitos biológicos y explorar a éstas como espacio de producción y reproducción de desigualdades de género. Objetivo: Explorar la presencia de desigualdades de género en relación a las tareas domésticas vinculadas a la alimentación y sus características en la población que asiste al Centro de Salud y Acción Comunitaria (CeSAC) Nº 21 del barrio Padre Mugica, Retiro (CABA), durante el primer semestre de 2021. Materiales y métodos: Se realizó la recolección y análisis de datos a partir de encuestas semiestructuradas y anónimas administradas por el encuestador. Resultados: La muestra está conformada por un total de 70 mujeres mayores de 18 años que conviven en unidad familiar con al menos un integrante de género masculino. Las mujeres son las principales responsables de las tareas domésticas vinculadas a la alimentación en las unidades familiares, realizando la elección del menú familiar, la compra, almacenamiento y cocción de los alimentos y el lavado de vajilla y utensilios. Conclusiones: Las tareas domésticas vinculadas a la alimentación están distribuidas injustamente entre los miembros de las familias, siendo las mujeres las que asumen éstas tareas en su mayoría, evidenciando la persistencia de modelos socioculturales y estereotipos de género. Es fundamental el rol de los profesionales de la alimentación como educadores y educadoras para detener la reproducción de las desigualdades de género vinculadas a las tareas alimentarias.

IntroductionNeurostimulation applied from deep brain stimulation (DBS) electrodes is an effective therapeutic intervention in patients suffering from intractable drug-resistant epilepsy when resective surgery is contraindicated or failed. Inhibitory DBS to suppress seizures and associated epileptogenic biomarkers could be performed with high-frequency stimulation (HFS), typically between 100 and 165 Hz, to various deep-seated targets, such as the Mesio-temporal lobe (MTL), which leads to changes in brain rhythms, specifically in the hippocampus. The most prominent alterations concern high-frequency oscillations (HFOs), namely an increase in ripples, a reduction in pathological Fast Ripples (FRs), and a decrease in pathological interictal epileptiform discharges (IEDs).Materials and methodsIn the current study, we use Temporal Interference (TI) stimulation to provide a non-invasive DBS (130 Hz) of the MTL, specifically the hippocampus, in both mouse models of epilepsy, and scale the method using human cadavers to demonstrate the potential efficacy in human patients. Simulations for both mice and human heads were performed to calculate the best coordinates to reach the hippocampus.ResultsThis non-invasive DBS increases physiological ripples, and decreases the number of FRs and IEDs in a mouse model of epilepsy. Similarly, we show the inability of 130 Hz transcranial current stimulation (TCS) to achieve similar results. We therefore further demonstrate the translatability to human subjects via measurements of the TI stimulation vs. TCS in human cadavers. Results show a better penetration of TI fields into the human hippocampus as compared with TCS.SignificanceThese results constitute the first proof of the feasibility and efficiency of TI to stimulate at depth an area without impacting the surrounding tissue. The data tend to show the sufficiently focal character of the induced effects and suggest promising therapeutic applications in epilepsy.

[it] Il racconto della conquista del potere a Tebe da parte di Lico, fornito dalla Biblioteca, presenta alcuni elementi che sembrano far riferimento a istituti propriamente politici. L’elezione a polemarco, in particolare, può alludere a eventi storici della Beozia di IV secolo a. C. Tale allusione rappresenta un chiaro anacronismo rispetto all’universo che fa da sfondo ai racconti del mitografo, ma, in questo caso, non risulta estranea allo sviluppo narrativo della sezione in cui si trova inserita. Evidenziando una differenza qualitativa tra la sovranità legittima dei Cadmei e quella illegittima di Lico, Zeto e Anfione, il riferimento alla polemarchia contribuisce al piano compositivo dello ps. Apollodoro, che si fonda sulla continuità genealogica. Per tale ragione, l’anacronismo può essere qui considerato il risultato di una scelta autoriale, che mostra come anche i mitografi abbiano giocato un ruolo nell’iterazione tra tempo mitico e passato storico che si riscontra all’interno delle loro opere.

El catálogo de los pretendientes de Penélope transmitido por Apolodoro presenta un caso interesante para estudiar el origen y el funcionamiento de las listas de nombres en la tradición erudita y mitográfica griega. Apolodoro menciona 129 pretendientes, frente a los 14 que aparecen nombrados en la Odisea, un hecho que, unido a la poca consistencia mitológica de estos personajes fuera del poema homérico, parece relegar el catálogo al campo de la simple invención libre, más que a la verdadera tradición mítica. Sin embargo, el estudio de los nombres de la lista y la comparación con otros catálogos, en parte transmitidos por papiros, permite reconocer algunos de los criterios utilizados por el compilador para construir la lista, como la interpretación del propio texto de Homero, y algunas estrategias compositivas que se pueden comparar con la práctica del centón. En este sentido, podemos apreciar cómo, también en este caso especial, la creación erudita tiene una relación muy fuerte con la tradición.

In epilepsy, the most frequent surgical procedure is the resection of brain tissue in the temporal lobe, with seizure-free outcomes in approximately two-thirds of cases. However, consequences of surgery can vary strongly depending on the brain region targeted for removal, as surgical morbidity and collateral damage can lead to significant complications, particularly when bleeding and swelling are located near delicate functional cortical regions. Although focal thermal ablations are well-explored in epilepsy as a minimally invasive approach, hemorrhage and edema can be a consequence as the blood-brain barrier is still disrupted. Non-thermal irreversible electroporation (NTIRE), common in many other medical tissue ablations outside the brain, is a relatively unexplored method for the ablation of neural tissue, and has never been reported as a means for ablation of brain tissue in the context of epilepsy. Here, we present a detailed visualization of non-thermal ablation of neural tissue in mice and report that NTIRE successfully ablates epileptic foci in mice, resulting in seizure-freedom, while causing significantly less hemorrhage and edema compared to conventional thermal ablation. The NTIRE approach to ablation preserves the blood-brain barrier while pathological circuits in the same region are destroyed. Additionally, we see the reinnervation of fibers into ablated brain regions from neighboring areas as early as day 3 after ablation. Our evidence demonstrates that NTIRE could be utilized as a precise tool for the ablation of surgically challenging epileptogenic zones in patients where the risk of complications and hemorrhage is high, allowing not only reduced tissue damage but potentially accelerated recovery as vessels and extracellular matrix remain intact at the point of ablation.

In patients with focal drug-resistant epilepsy, electrical stimulation from intracranial electrodes is frequently used for the localization of seizure onset zones and related pathological networks. The ability of electrically stimulated tissue to generate beta and gamma range oscillations, called rapid-discharges, is a frequent indication of an epileptogenic zone. However, a limit of intracranial stimulation is the fixed physical location and number of implanted electrodes, leaving numerous clinically and functionally relevant brain regions unexplored. Here, we demonstrate an alternative technique relying exclusively on non-penetrating surface electrodes, namely an orientation-tunable form of temporally interfering (TI) electric fields to target the CA3 of the mouse hippocampus which focally evokes seizure-like events (SLEs) having the characteristic frequencies of rapid-discharges, but without the necessity of the implanted electrodes. The orientation of the topical electrodes with respect to the orientation of the hippocampus is demonstrated to strongly control the threshold for evoking SLEs. Additionally, we demonstrate the use of Pulse-width-modulation of square waves as an alternative to sine waves for TI stimulation. An orientation-dependent analysis of classic implanted electrodes to evoke SLEs in the hippocampus is subsequently utilized to support the results of the minimally invasive temporally interfering fields. The principles of orientation-tunable TI stimulation seen here can be generally applicable in a wide range of other excitable tissues and brain regions, overcoming several limitations of fixed electrodes which penetrate tissue and overcoming several limitations of other non-invasive stimulation methods in epilepsy, such as transcranial magnetic stimulation (TMS).